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HE  ELECTROMETRIC  TITRATION  OF  THE 
PLASMA  AS  A  MEASURE  OF  ITS 
ALKALINE  RESERVE 


DISSERTATION 

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PURE    SCIENCE    OF   COLUMBIA   UNIVERSITY 


BY 

GLENN  E.  CULLEN 


1 


NEW  YORK 
1917 


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Hiljrarp 


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THE  ELECTROMETRIC  TITRATION  OF  THE 
PLASMA  AS  A  MEASURE  OF  ITS 
ALKALINE  RESERVE 


BY 
GLENN  E.  CULLEN 


This  work  was  performed  under  the  auspices  of  the  Biochemical  Depart- 
ment of  Columbia  University,   in  partial  fulfilment  of  the  require- 
ments for  the  degree  of  Doctor  of  Philosophy  in  the  Faculty 
of  Pure  Science  of  Columbia  University 


Reprinted  from 

THE  JOURNAL  OF  B-IOLOGICAL  CHEMISTRY 
Vol.  XXX,  No.  2,  June,  1917 


Reprinted  from  The  Journal  of  Biological  Chemists  t,  Vol.  XXX,  No.  2,  1917 


STUDIES  OF  ACIDOSIS. 

III.  THE  ELECTROMETRIC  TITRATION  OF  PLASMA  AS  A 
MEASURE  OF  ITS  ALKALINE  RESERVE. 

By  GLENN  E.  CULLEN. 

{From  the  Hos-pilal  of  The  Rockefeller  Institute  for  Medical  Research.) 

(Received  for  publication,  April  26,  1917.) 

It  has  been  definitely  established  that  the  reaction  of  the  blood 
is,  under  normal  conditions,  constant  (Limdsgaard,  1912)  and 
may  be  kept  constant  even  under  pathological  concUtions  in- 
volving great  lowering  of  the  alkaline  reserve  (Michaehs,  p.  10.5; 
Benedict,  1906;  Peabody,  1914;  for  more  detailed  discussion  see 
Paper  I  of  this  series).  Consequently,  the  hydrogen  ion  concen- 
tration (CH)~-of  the  blood  as  drawn  from  the  veins  cannot  be 
taken  as  an  indicator  of  the  alkaline  reserve. 

We  may  expect,  however,  that  when  a  given  amount  of  acid  is 
added  to  the  blood,  the  resultant  change  in  Ch  '^'iH  be  greater 
the  less  the  reserve  alkali;  or  conversely,  that  less  acid  will  be 
necessary  to  produce  a  given  increase  in  Cg.  The  latter  prin- 
ciple is  essentially  that  used  in  methods  for  titration  of  the  blood 
with  indicators,  acid  being  added  until  the  Ch  is  reached  at 
wh^ch  the  indicator  changes  color;  and  titration  methods  have 
contributed  greatly  to  our  knowledge  concerning  the  alkaline 
reserve  of  the  blood  and  its  changes  in  acidosis  (Jaksch,  Magnus- 
Levy,  Pembrey,  and  Spriggsj.  The  interpretation  of  such  re- 
sults, however,  is  clouded  by  two  deficiencies  inherent  in  the 
method.  First,  the  indicators  (Bjerrum,  1915),  such  as  methyl 
orange,  which  can  be  used  to  titrate  carbonates  as  alkah  change 
color  at  such  a  high  Ch  that  the  titration  measures,  in  addition 
to  the  bicarbonate,  also  an  acid  binding  power  of  the  proteins 
quite  out  of  proportion  to  the  amounts  of  acid  which  these  sub- 
stances can  bind  "within  the  Umits  of  Ch  possible  in  life  (the 
phosphates  of  whole  blood  also  act  as  buffers  like  proteins,  but 
they  play  a  minimal  role  in  plasma) .     Second,  the  proteias  dimin- 

369 


370  Electrometric  Titration  of  Plasma 

ish  by  their  buffer  effect  and  by  absorption  of  indicator  the  sharp- 
ness of  the  end-points,  and  thereby  decrease  the  accuracy  of  the 
titrations.  Attempts  to  overcome  these  difficulties  by  precipi- 
tating the  proteins  with  neutral  agents  such  as  ammonium  sulfate 
are  criticized  because  the  precipitated  protein  carries  down  with 
it  a  considerable  part  of  the  alkali  (Hoppe-Sejder).  Of  the  above 
two  difficulties  the  first  is  inherent  in  every  mode  of  titrating 
blood  against  strong  acids.  The  second,  however,  can  be  avoided 
by  determining  the  Ch  of  the  end-point  electrometrically 
instead  of  by  indicators,  so  that  even  with  small  amounts  of  blood 
or  plasma  results  reproducible  with  a  high  degree  of  accuracy 
can  be  obtained.  The  present  paper  presents  the  results  of  an 
attempt  to  develop  the  electrometric  titration  into  a  form  prac- 
ticable for  use  with  normal  and  pathological  plasmas, — and  the 
comparison  of  the  method  so  developed  with  the  determination  of 
the  carbon  dioxide  combining  capacity  of  the  plasma  (Van  Slyke 
and  Cullen,  1917),  and  of  the  carbon  dioxide  tension  of  the 
alveolar  air  (see  Paper  VI  of  this  series) . 

The  principles  of  the  gas  chain  method  and  its  practice  have 
been  so  thoroughly  reviewed  in  recent  literature  (Soerensen, 
1912;  Hildebrand,  1913;  Michaelis,  1914;  Clark  and  Lubs,  1916) 
that  only  the  necessary  details  are  given  here. 

Apparatus'. 

All  determinations  of  the  H+  concentration  were  made  by  use 
of  the  well  known  gas  chain. 

Saturated 
KCl 

The  mercury  for  the  calomel  cells  was  purified  in  the  wet  way, 
distilled  three  times  by  Hulett's  method  (1911),  and  filtered. 
The  calomel  was  made  from  this  mercury  by  the  method  of  Loomis 
and  Acree  (1911)  .^  The  n/10  KCl  solution  was  prepared  by 
weight  from  recrystalhzed  Kahlbaum's  KCl  and  the  standardi- 

^  Electrodes  prepared  from  this  calomel  have  not  been  very  satisfac- 
tory. In  later  work  with  the  gas  chain  the  calomel  has  been  prepared 
electrolytically  as  described  by  Ellis  (1916).  The  calomel  has  been  kept 
under  acid  and  prepared  for  use  by  washing  by  decantation  only.  Cells 
prepared  from  such  calomel  remain  entirely  constant  for  long  periods. 


Hg 


HgCl 


n/10  KCl 


Solution 


Ho 


Pt 


G.  E.  CuUen  371 

zation  verified  by  chloride  determinations  by  the  McLean  and 
Van  Slyke  method. 

The  hydrogen  was  taken  from  tanks  of  the  Standard  Oxygen 
Company  and  was  washed  thi'ough  solutions  of  HgCl2,  KMnO^, 
pyrogallol  (twice),  dilute  H2SO4,  and  water.  This  proved  to  be 
a  convenient  and  satisfactory  source  of  hydrogen. 

The  electrodes  were  made  from  No.  16  and  No.  18  platinum 
wire  sealed  into  glass  tubes  and  platinized  with  platinum  black. 
Small  Clark  electrode  vessels  of  about  2  cc.  capacity  were  used, 
together  with  the  ingenious  Clark  shaking  de"vice  (Clark,  1915). 
This  vessel  is  similar  in  principle  to  that  of  Hasselbalch  (1911, 
1913),  but  is  superior  to  it  both  practically  and  theoretically. 
It  is  designed  to  give  maximum  surface  of  solution  and  elimination 
of  dead  space,  and  to  reduce  the  contact  potential  between  the 
solution  and  saturated  KCl  solution  to  a  negligible  quantity. 
It  is  easily  manipulated,  requires  only  a  small  amount  of  fluid, 
and  gives  such  thorough  contact  of  solution  and  electrode  that 
.  equihbrimn  is  established  inside  of  a  few  minutes.  This  appa- 
ratus is  especially  convenient  when  working  with  carbon  dioxide 
containing  fluids,  for  it  allows  easy  and  economical  renewal  of 
the  solution  wdthout  change  of  hydrogen,  the  procedure  proposed 
by  Hasselbalch.  The  substitution  of  a  60°  3-way  stop-cock  with 
a  2-way  key  for  the  lower  stop-cock  of  the  Clark  vessel  is  a 
decided  convenience. 

Several  calomel  electrodes  were  kept  on  hand,  and  compared 
frequently  with  one  another.  An  absolute  standard  was  thus 
maintained,  and  the  readings  corrected  with  it.  Weston  cells 
cahbrated  by  the  Bureau  of  Standards  gave  the  standard  poten- 
tial. The  readings  were  taken  during  the  earUer  part  of  the 
■work  with  a  bridge  of  1,110  ohms  resistance  boxes  and  electrom- 
eter as  zero  point  instrument.  The  external  resistance  was  so 
adjusted  that  ohms  equalled  milHvolts.  Later  a  Leeds  and 
Northrup  potentiometer  with  a  galvanometer  as  zero  point  instru- 
ment was  installed. 

The  determinations  were  run  at  room  temperature,  18-24°,  and 
temperature  corrections  applied.  The  accuracy  of  the  entire 
determination  was  tested  often  by  means  of  Soerensen's  standard 
phosphate  and  Walpole's  standard  acetate  mixtures  of  known 
hydrogen  ion  concentration. 


372  Electrometric  Titration  of  Plasma 

The  n/50  acid  used  in  the  titrations  was  prepared  by  weight  from 
a  standard  HCl  prepared  by  Hulett  and  Bonner's  (1909)  method 
and  checked  by  gravimetric  silver  chloride  determinations. 

Hasselbalch  and  Gammeltoft  (1915)  report  that  freshly  plat- 
inized electrodes  are  essential.  Our  experience  entirely  corrobo- 
rates this  observation.  The  electrodes  were  always  carefully 
cleaned  before  each  determination  in  accordance  with  the  follow- 
ing routine.  The  washed  electrodes  were  placed  as  cathode  in 
the  reducing  vessel  containing  5  per  cent  H2S0^  for  3  minutes 
where  the  bubbling  hydrogen  removed  a  considerable  quantity 
of  precipitated  protein  that  could  not  be  washed  off.  Then  they 
were  rinsed  with  water,  placed  as  cathode  in  the  platinic  chloride 
solution  for  2  minutes,  rinsed,  returned  to  the  reducing  vessel 
for  3  minutes,  rinsed  thoroughly  with  tap  water,  and  finally 
with  distilled  water.  The  electrodes  were  often  checked  against 
the  standard  solutions. 

Calculation  of  Results. 

All  H+  concentrations  are  expressed  by  Soerensen's  symbol 
pH,  the  negative  Briggs  logarithm  of  the  hydrogen  ion  concen- 
tration. pH  values  are  more  easily  visualized  and  plotted  than 
those  of  Ch,  the  actual  hydrogen  ion  concentration.  The 
equation  for  the  calculation  of  results  was: 

1  „  E- 0.337 

log  -7^  =  pH  = 


0.0577  [1  +  (t°  -  18°)  0.0002] 

In  our  work  the  variations  in  potential  and  temperature  were 
such  that  it  was  most  convenient  to  construct  tables  giving  pH 
directly  from  the  observed  readings.  We  used  the  rounded  value- 
of  0.337  for  the  n/10  calomel  electrode  adopted  by  the  Potential 
Commission  (Auerbach). 

Preparation  of  Solution. 

All  our  determinations  have  been  made  on  plasma  rather  than 
whole  or  defibrinated  blood;  because  removal  of  the  corpuscles 
ehminates  the  greater  part  of  the  oxygen  and  consequently  allows 
much  quicker  reduction  of  the  solution  by  the  hydrogen  electrode. 


G.  E.  CuUen  373 

The  blood  was  drawn  into  a  tube  containing  a  small  amount 
of  powdered  potassium  oxalate  (always  less  than  0.5  per  cent)  to 
prevent  clotting,  centrifuged  at  once,  and  the  plasma  pipetted 
off.  Experiments  proved  that  the  oxalate  had  no  effect  on  the 
determination.  If  it  was  impossible  to  run  the  determination  at 
once,  the  plasma  was  placed  in  a  stoppered  paraffined  tube  in 
the  refrigerator. 

In  comparing  the  alkaline  reserve  of  different  plasmas  by  titra- 
tion with  acid,  two  methods  are  available.  First,  the  amount  of 
acid  required  to  bring  the  plasma  to  a  definite  H+  concentration 
may  be  determined  by  a  series  of  determinations  and  consequent 
plotting  of  the  titration  curve.  Or,  second,  the  H+  concentra- 
tion resulting  from  the  addition  of  an  arbitrarily  fixed  amount 
of  acid  may  be  found.  This  is  the  most  economical,  both  of  time 
and  blood,  the  deciding  considerations  when  series  of  observa- 
tions on  a  number  of  patients  are  desired.  We  therefore  used 
the  former  only  to  select  suitable  conditions  to  use  in  this 
investigation. 

However,  since  the  initial  reaction  of  all  plasmas  is  practically 
constant  and  the  titration  curve  is  almost  a  straight  line,  it  is 
entirely  possible  to  construct  the  curve  from  one  determination 
and  from  it  determine  the  amount  of  acid  required  to  bring  the 
plasma  to  any  desired  reaction. 

H2CO3 

It  is  evident  from  the  analysis  of  the  equilibrium  •     ^^^  that 

JN  axlUUs 

all  samples  must  be  brought  to  a  definite  CO2  content.  The  con- 
ditions under  which  the  blood  is  drawn,  the  time  elapsing  before 
determination,  etc.,  are  so  variable  that  the  plasma  cannot  be 
used  as  it  is.  Its  CO2  content  must  either  be  fixed  under  definite 
conditions,  or  the  CO2  must  be  removed. 

Two  procedures  have  been  followed.  The  first  was  worked 
out  for  and  used  throughout  the  investigation  of  the  first  series 
of  experiments  on  diabetic  acidosis;  the  second  was  developed  on 
the  basis  of  experience  with  that  series. 

Technique  of  Determination. 

Procedure  A. — It  was  found  that  two  successive  shakings  in 
an  evacuated  vessel,  as  described  in  the  next  paragraph,  reduced 
the  CO2  content  to  a  fairly  constant  level.     Experiments  with 


374  Electrometric  Titration  of  Plasma 

n/50  HCl  showed  that  more  than  three  volumes  of  this  acid  per 
volume  of  plasma  precipitated  some  of  the  proteins.  The  addition 
of  one  volume  of  n/50  acid  to  one  volume  of  plasma  (Fig.  1) 
brought  normal  plasma  to  about  the  neutral  point.  Plasma  with 
less  than  normal  alkaline  reserve  would,  under  the  same 
conditions,  fall  on  the  acid  side  of  the  neutral  line. 

The  oxalated  blood  was  centrifuged  and  the  plasma  pipetted 
off.  About  3  cc.  of  the  plasma  were  placed  in  a  300  cc.  separatory 
funnel,  which  was  evacuated  by  means  of  a  water  aspirator  to  a 
pressure  of  about  20  mm.  The  funnel  was  then  rotated  for  3 
minutes  to  insure  maximum  surface  and  permit  the  escape  of 
carbon  dioxide  from  the  solution.  Air  was  then  admitted,  the 
funnel  was  evacuated,  and  was  again  rotated  for  3  minutes. 
Exactly  1  cc.  of  this  plasma  was  then  measured  into  a  3  cc.  drop- 
ping funnel,  and  1  cc.  of  n/50  HCl  added  (cahbrated  1  cc.  pipettes 
were  used  for  both  acid  and  plasma);  the  funnel  was  closed  by 
means  of  a  small  rubber  stopper  and  the  solution  mixed,  without 
shaking.  The  mixed  solution  was  then  allowed  to  flow  through 
a  small  piece  of  rubber  tubing  into  the  Clark  electrode,  displacing 
part  of  the  hydrogen  with  which  the  vessel  had  been  filled.  The 
care  taken  in  mixing  and  introducing  the  acidified  solution  was 
to  prevent  loss  of  CO2.  The  vessel  was  then  shaken  for  3  or  4 
minutes,  the  electrode  adjusted  to  minimum  contact,  and  the 
potential  read.  The  vessel  was  shaken  again  3  or  4  minutes,  a 
fresh  contact  with  the  saturated  KCl  solution  was  made,  another 
reading  taken,  and  the  process  was  continued  until  equilibrium 
was  reached,  which  usually  was  at  the  second  or  third  reading. 

Procedure  B. — The  method  outlined  under  A  is  open  to  the  ob- 
jection that  careful  attention  is  required  to  bring  the  carbon 
dioxide  to  the  arbitrary  level.  This  possibihty  of  error  can  be 
eliminated  by  adding  enough  acid  to  complete  the  reaction 
NaHCOs  +  HCl  =  NaCl  +  H2CO3,  and  then  removing  aU  the 
carbon  dioxide  by  evacuation.  The  carbon  dioxide  tension  of 
the  plasma  is  thus  eliminated  as  a  factor  in  the  results,  and  the 
hydrogen  ion  concentration  is  dependent  on  the  equilibrium  be- 
tween the  plasma  buffers,  chiefly  the  proteins,  and  the  excess  of 
acid  not  neutrahzed  by  bicarbonate.  It  was  found  that  the  addi- 
tion of  two  volumes  of  n/50  HCl  to  one  of  plasma  was  sufficient  to 
effect  complete  decomposition  of  the  bicarbonate,   and   the  re- 


G.  E.  CuUen 


375 


suiting  solution  after  removal  of  the  carbon  dioxide  showed  a 
Ch  of  about  10"^-^  (pH  =  5.6).  At  tiiis  point  the  equihbrium 
in  the  electrode  vessel  is  obtained  much  quicker  than  at  the  neu- 
tral point.  This  procedure  has,  over  A,  the  advantages  of  greater 
rapidity,  the  use  of  smaller  amounts  of  plasma,  and  the  elimina- 
tion of  variations  in  the  carbon  dioxide  content  as  a  source  of 
error.  It  has  the  disadvantage,  compared  with  procedm-e  A, 
in  that  the  differences  in  pH  corresponding  to  given  differences 
in  ''alkaUne  reserve"  are  not  so  great. 

In  procedure  B  two  volumes  of  n/50  HCl  are  added  to  one  of 
plasma  (the  amounts  being  usually  2  and  1  cc.  respectively)  in  a 
small  separatory  funnel,  25  to  100  cc,  the  solution  is  exhausted 
with  a  water  aspirator  to  about  20  mm.,  and  agitated  for  1  min- 
ute. One  exhaustion  completely  removes  the  carbon  dioxide. 
The  solution  is  then  transferred  to  the  electrode  vessel  by  a  pipette, 
allowed  to  displace  part  of  the  hydrogen,  and  the  reading  obtained 
in  the  same  manner  as  in  A. 


EXPERIMENTAL. 

The  Determination  of  the  Optimum  Amouiits  of  n/oO  Acid. 

Samples  of  oxalated  plasmas  were  exhausted  twice  with  the  water 
aspirator  and  the  H+  of  the  exhausted  plasma  determined.  Then 
a  series  of  determinations  was  made  varying  the  ratio  of  acid  and 
plasma  volume  as  shown  in  Fig.  1. 


/fc/-CcWo.o2  per/cc.p/os/rto  (cog  exhausted) 
Fig.  1. 


376 


Electrometric  Titration  of  Plasma 


It  is  evident  that  the  addition  of  one  volume  of  n/50  acid  to  one 
volume  of  plasma  brings  normal  plasma  to  about  the  neutral  point. 
The  acidosis  plasma  affords  an  extreme  example  of  diminished 
alkaline  reserve. 


Determination  of  the  Number  of  Exhaustions  Required  in  Water 

Aspirator. 

Samples  of  plasma  were  saturated  with  alveolar  air  (5.5  per 
cent  CO2),  portions  were  placed  in  separatory  funnels,  and  ex- 
hausted on  a  water  aspirator  to  about  20  nun.  for  periods  of  3 
minutes  each.  During  the  exhaustion  the  funnels  were  rotated 
constantly  to  expedite  the  escape  of  the  CO2  from  the  solution. 
Air  was  admitted  to  the  funnels  between  exhaustions.  1  cc.  por- 
tions were  then  mixed  with  1  cc.  portions  n/50  HCl  in  3  cc.  drop- 
ping funnels,  as  described  above,  and  the  contents  run  into  the 
electrode  vessels  (Table  I) . 

TABLE  I. 

Number  of  Exhaustions  Needed  for  Procedure  A.     pH  after  Adding  One 
Volume  n/50  HCl  to  Exhausted  Plasma. 


Human  plasma. 

Treatment  of  sample. 

Saturated  with 
5.5  per  cent  CO2. 

Exhausted 
once.  * 

Exhausted 
twice. 

Exhausted 
three  times. 

pH 

pH 

pH 

pH 

1 

6.42 

6.67 

6.69 

6.69 

2 

6.66 

6.76 

6.78 

6.78 

3 

6.47 

6.63 

6.63 

6.45 

6.62 

6.62 

4 

7.03 

7.03 

.7.03 

*  Each  exhaustion  lasted  3  minutes. 

It  appeared  from  the  above  that  two  exhaustions  were  sufficient 
for  our  purpose,  and  it  was  desirable  to  avoid  as  far  as  possible 
concentrating  the  plasma  by  evaporation.  Later,  however,  the 
perfection  of  Van  Slyke's  CO2  apparatus  furnished  an  accurate 
and  convenient  means  of  checking  the  above  experiments.  The 
amounts  of  carbon  dioxide  remaining  after  successive  exhaustions 
were  determined.  The  plasma  was  placed  in  large  separatory 
funnels,  the  exhaustions  were  carried  out  as  described  under  pro- 


G.  E.  Cullen 


377 


cedure  A,  and  a  1  cc.  sample  was  removed  for  analysis  after  each 
exhaustion  (Table  II). 


TABLE  II. 


Number   of  Exhaustions   Needed  for   Procedure   A.     Total   Residual   CO2 
Determined  by  Van  Slyke's  Method.     Corrected  to  0",  760  Mm. 


a 

to 

CO 

2  remaining  after 

g 

6  . 

d 

d  . 

a 

6 

s 

6 

d 

0 

ja 

0  a 

0  s 

0  d 

0  d 

0 

0  d 

Human 

"m 

"to 

0 

0 

■+^ 

0 

plasma. 

2^ 

a 

"og 

3 

og 

OJ 

°g 

o3 

0;^ 

^ 

'o'i 

«  3 

11 

II 

0  oa 

J3 

fi5 

^ 
g 

M 

II 

0   CO 

J3 

11 

■§" 

« 

&■§ 

-0 

Sta 

"H 

gts 

J3 

0  " 

_« 

§■§ 

cc 

" 

P-, 

cs 

Ph 

CO 

Ph 

■* 

(^ 

to 

^ 

cc. 

cc. 

cc. 

cc. 

cc. 

cc. 

G 

0.79 

0.60 

76.2 

0.54 

68 

0.49 

62 

0.48 

60 

0.45 

57 

A 

0.72 

0.53 

73 

0.43 

60 

0.40 

56 

0.38 

53 

0.38 

51 

An 

0.75 

0.55 

73 

0.45 

60 

0.41 

54 

0.38 

51 

0 

0.775 

0.57 

74 

0.52 

67 

0.46 

59 

0.43 

55 

0.40 

51 

It  is  evident  from  Table  II  that  exhaustion  was  not  complete. 
This  was  expected.  However,  the  variations  after  two  exhaus- 
tions were  so  small  in  their  effect  on  pH,  as  demonstrated  in  Table 
I,  that  accurately  reproducible  results  are  obtainable  when  two 
exhaustions,  carried  out  as  described,  are  used  as  the  arbitrary 
standard. 

That  the  arbitrarily  selected  double  exhaustion  approximates 
to  a  constant  carbon  dioxide  content  is  also  evident  from  the  curves 
constructed  from  these  values  in  Fig.  2. 

The  carbon  dioxide  as  a  source  of  error  has  been  entirely  elim- 
inated in  procedure  B  by  the  use  of  larger  amounts  of  acid  and 
exhaustion  after  its  addition.  The  following  experiment  shows 
this  (Table  III). 

Two  volumes  of  n/50  acid  were  added  to  one  volume  of  plasma 
in  a  separatory  funnel.  The  funnel  was  exhausted  to  about  20 
mm.  for  1  minute,  with  constant  rotation.  1  cc.  was  taken  for 
analysis  and  the  exhaustion  repeated. 

The  amounts  of  residual  gas  in  column  3  are  entirely  com- 
parable with  the  "dissolved  air"  correction  in  this  method; 
therefore  no  measurable  amounts  of  carbon  dioxide  were  present. 


378 


Electrometric  Titration  of  Plasma 


£xhaujfions 


4         s 

Fig.  2.      From  Table  II. 


TABLE  III. 


Number  of  Exhaustions  in  Water  Aspirator  Needed  after  Adding  Two  Vol- 
umes of  n/50  HCl.     Dissolved  Gases  Determined  by  Van  Slyke's 
Method.     30°  and  762  Mm. 


Sample  plasma. 

Exhausted 

3'  with  shaking. 

Gas  observed. 

Dissolved  air 

calculated  as 

present. 

CO2  present. 

Mixed  normal 

cc. 

0.04 

0.04 
0.045 
0.04 
0.05 

cc. 

0.044 

0.044 
0.044 
0.044 
0.044 

cc. 

0.000 

Same  saturated  with  6.3  per  cent 
CO2 

0.000 

A 

0  000 

Dog 

0.000 

H 

0  000 

Comparison  of  Two  Procedures  for  Removing  Carbon  Dioxide. 

Hydrogen  ion  concentrations  were  determined  on  two  plasmas. 
Each  was  then  divided  in  two  portions,  one  of  which  was  placed 
in  a  separatory  funnel  and  was  exhausted  3  minutes  as  in 
procedure  A.  1  cc.  samples  were  then  mixed  with  various  vol- 
umes of  n/50  acid  and  the  resulting  reaction  was  determined. 

To  samples  of  the  other  portions  in  separatory  fimnels  varying 
volumes  of  n/50  acid  were  added  and  the  mixtures  exhausted 


G.  E.  CuUen 


379 


for  1  minute.  The  results  are  given  in  Table  IV  and  plotted 
in  Figs.  3  and  4;  it  is  evident  that  the  two  series  differ  but 
little. 

TABLE  IV. 
Comparison  of  Procedures  A  and  B. 


Plasma 

n/50 
acid  per  cc.  plasma. 

A 

(exhausted  twice  before 

adding  acid). 

B 

(exhausted  once  after 
adding  acid). 

P. 

cc. 

pH  =  8.63. 

0.5 

7.73 

7.56 

7.74 

7.58 

1.0 

6.74 
6.74 

6.68 

2.0 

5.43 

5.34 

5.42 

5.33 

3.0 

4.54 

4.40 

4.53 

4.40 

M. 

pH  =  8.61. 

0.5 

7.76      . 

7.83 

1.0 

6.88 

.     6.87 

2.0 

5.47 

5.48 

Ccaoz  !/HClpsi'l<^^-  p/asmej  'P'  (norm at] 
Fig.  3. 


380 


Electrometric  Titration  of  Plasma 

9 


a   6 


C  C.  O.OZ  NHCI  percc.p/asma"M-(normo/) 

Fig.  4. 

Ex-periment  to  Determine  the  Effect  of  Oxalate  on  the  Titration  of 

Plasma. 

Solutions  of  m/10  phosphates  and  of  normal  plasma  were  made 
up  with  varying  concentrations  of  potassium  oxalate.  H+  con- 
centration determinations  were  made  as  indicated  in  Table  V. 
It  is  evident  that  in  plasma  oxalate  up  to  0.5  per  cent  does  not 
produce  an  appreciable  change  and  that  the  change  produced  by 
1  per  cent  is  within  the  allowable  limits  of  experimental  error. 
About  0.2  to  0.3  per  cent  is  ordinarily  sufficient  to  prevent 
clotting. 

'  TABLE  V. 

Effect  of  Oxalate. 


On  pH  of  m/10  phosphate 

solution 

concentration. 

On  pH  of  m/10  phosphate 

solution  +  1  vol.  n/50  HCl 

concentration. 

On  pH  of  normal  plasma 

treated  by  procedure  B 

(2  vol.  n/50  acid  added) 

concentration. 

K  oxalate. 

pH. 

K  oxalate. 

pH. 

K  oxalate. 

pH. 

per  cent 
0 

0.2 
0.6 
1.0 
1.6 
2.0 

7.50 
7.47 
7.47 
7.44 
7.45 
7.94 

per  cent 

0 

0.25 
0.5 
1.0 

6.74 
6.74 
6.74 
6.72 

per  cent 

0 

0.5 

1.0 

2.0 

4.0 

5.38 
5.38 
5.39 
5.45 
5.53 

G.  E.  CuUen 


381 


Effect  of  Renewing  Solutions  in  Electrodes. 

Hasselbalch  pointed  out  the  possibility  of  renewing  succes- 
sively the  solutions  in  the  electrode  without  renewing  the  Ha  as 
a  means  of  bringing  the  CO2  content  of  the  electrode  gas  to  equi- 
hbrium  with  that  of  the  solution.  The  following  experiment 
(Table  VI)  shows  that  this  precaution  is  unnecessary  with  the 
small  amount  of  residual  CO2  present  under  procedure  A. 

TABLE  VI. 

Effect  of  Renewing  Solution  without  Change  of  Hn  Atmosphere.     New  Solu- 
tions Were  Run  into  the  Electrode  Vessel  Displacing  the   Used 
Solution  without  Changing  the  Hi  Bubble. 


Plasma. 


pH  of  1st  determination. 
pH  of  renewed  solution. . 


E. 

s. 

u. 

H. 

M. 

M.  2. 

8.13 
8.14 

7.11 
7.11 

6.48 
6.48 

7.03 
7.03 

6.55 

6.58 

6.89 
6.91 

6.99 
6.99 


Accuracy  of  the  Method. 

Clark  has  pointed  out  the  possibiUty  of  accuracy  attainable 
with  his  electrode.  With  plasma  we  have  considered  1  millivolt 
=  0.02  pH  our  permissible  error.  This  amount  is  very  small  in 
comparison  with  the  gross  differences  we  have  obtained  in  the 
clinical  studies. 

Table  VII  gives  samples  of  the  results  obtained  in  dupHcate 
determinations. 


Titration  of  Plasma  Containing  Lactic  and  ^-Oxybutyric  Acids. 

Since  a  diminished  alkaline  reserve  is  the  result  of  the  introduc- 
tion of  abnormal  acid  products  of  metaboHsm,  it  seemed  desir- 
able to  investigate  the  effects  of  adding  such  acids  to  a  normal 
plasma  in  vitro.  The  results  of  such  experiments  are  shown  in 
Tables  VIII  and  IX,  and  Figs.  5  and  6.  These  experiments  were 
performed  as  follows: 

Experiment  I.  Curves  A  and  B. — A  weighed  amount  of  acid 
was  added  to  a  portion  of  plasma  to  make  the  plasma  0.2  per 
cent  acid  solution.  This  solution  was  then  mixed  with  untreated 
plasma  in  varying  proportions  and  the  resulting  mixtures  were 


382 


Electrometric  Titration  of  Plasma 


TABLE  VII. 
Duplicate  DelerminalionsMade  loilh  Different  Electrodes  in  Different  Vessels. 


Procedure  A. 

Procedure  B 

Plasma 
(human) . 

Date. 

il 
H 

'-3 
Pi 

0. 

Plasma. 

Date. 

to 
a 

•3 

°C 

milli- 
volts 

°C. 

milli- 
volts 

A. 

May  15 

23 

723 

6.57 

Dog  VIII. 

25 

630 

4.96 

23 

722 

6.55 

23 

627.7 

4.96 

W. 

"     25 

24 

742 

6.87 

(( 

June 

14 

25 

627 

4.91 

Normal. 

23.5 

740 

6.85 

23 

626.6 

4.93 

V. 

"     26 

23 

744 

6.93 

v.*  (human). 

(( 

13 

25 

650.4 

5.30 

Normal. 

23 

744 

6.93 

26 
26 

652.5 
651.6 

5.33 
5.31 

M. 

"     23 

24 

749 

6.99 

26 

651.6 

5.31 

Normal. 

749,5 

7.00 

26.5 

652.3 

652.2 

5.32 
5.32 

H. 

March  21 

20 

723 

6.64 

21 

723 

6.62 

Dog  2  a. 

it 

10 

25 

26 

620 
622.6 

4.98 
4.91 

"   2  b. 

te 

10 

25 
26 

631.5 
632 

4.98 
4.97 

"   3. 

t( 

11 

22 

630 
630.1 

5.00 
5.00 

*  These  six  determinations  were  run  with  six  distinct  pipettes,  funnels, 
and  electrodes,  and  in  two  electrode  vessels. 

titrated  by  both  A  and  B  methods.  The  acids  were  analyzed  by 
adding  excess  n/7  NaOH,  warming  on  a  steam  bath  for  a  couple 
of  hours,  and  titrating  back  with  n/7  HCl  using  phenolphthalein. 


/9-Hydroxybutyric  acid  analyzed. 
Lactic  acid  analyzed 


per  cent 

100 
95.2 


Experiment  II.  Curve  C. — The  acids  used  in  the  preceding 
experiment  had  not  been  treated  to  remove  any  anhydride  that 
might  have  been  present;  the  experiment  was  therefore  repeated. 


G.  E.  CuUen 


383 


TABLE  VIII.  . 

Effect  of  Organic  Acids  on  the  Titration  Curve. 


Normality  of  organic  acid  on 
basis  of  plasma  volume  only. 


1  vol.  plasma  +  1  vol. 
n/50  acid. 
Curve  A. 


1  vol.  plasma  +  2  vol. 
n/oO  acid. 
Curve  B. 


/3-Hydroxybutyric  acid  (Fig.  5). 


PH 

pH 

0 

6.73 

5.34 

6.72 

5.35 

0.0094 

6.55 

5.16 

6.55 

5.16 

0.024 

5.84 

4.85 

5.84 

4.85 

0.047 

5.08 

4.58 

5.07 

4.57 

0.094 

4.59 

4.29 

4.58 

4.28 

0.189 

4.15 

4.00 
t           4.00 

Lactic  acid  (Fig.  6). 

0.011 

6.26 

4.94 

6.24 

4.94 

0.028 

5.355 

4.565 

5.345 

4.575 

0.056 

4.58 

4.18 
4.18 

0.11 

4.03 

3.83 

4.02 

3.83 

0.22 

3.64 

3.48 

3.65 

3.48 

0.225  gm.  of  lactic  acid  was  placed  in  a  flask  with  30  cc.  of  n/10 
sodium  hydroxide,  placed  on  the  steam  bath  for  2  hours,  50  cc. 
of  n/10  HCl  were  added,  and  the  solution  was  diluted  to  100  cc. 
The  solution  was  then  n  0.025  to  lactic  acid  and  n  0.02  to  hydro- 
chloric acid. 

2  gm.  of  CaZn  /S-oxybutyric  acid  salt  were  treated  with  three- 
fourths  of  its  equivalent  sulfuric  acid  and  the  hberated  acid  was 
extracted  with  ether  in  a  wet  extractor.  The  ether  was  evapo- 
rated off  .over  water  and  the  solution  diluted  to  100  cc.  The 
amount  of  acid  was  titrated  with  sodium  hydroxide  as  in  lactic 


THE  JOURNAL   OP   BIOLOGICAL  CHEMISTRY,    VOL.   XXX,    NO.  3 


384 


Electrometric  Titration  of  Plasma 


acid.  0.130  gm.  of  tliis  acid  was  then  treated  with  15  cc.  of  n/10 
sodium  hydroxide  heated  on  the  steam  bath  for  2  hours,  25  cc. 
of  n/10  HCl  were  added,  and  the  solution  was  dihited  to  50  cc. 
Tins  sokition  was  then  n  0.025  to  /3-oxybutyric  acid  and  n  0.02  to 
hj^drochloric  acid. 

TABLE  IX. 
Effect  of  Organic  Acid  on  the  Titration  Curve. 


Solution  A. 

1  vol.  plasma  + 

2  vol.  n/50  HCl. 

Solution  B.* 

Normality  of 
organic  acid  on 
basis  of  plasma 

volume  only. 

Lactic  acid. 

Curve  C, 

Fig.  6. 

;3-Hydroxybut5n:ie 

acid.  Curve  C, 

Fig.  5. 

pH 

pH 

_ 

0 

0 

4.55 

4.55 

4.0 

0.5 

0.0055 

4.41 

4.45 

4.0 

1.0 

0.01 

4.32 

4.39 

4.0 

2.0 

0.0166 

4.20 

4.31 

3.0 

3.0 

0.025 

4.09 

4.24 

1.0 

3.0 

0.037 

3.96 

4.15 

0 

♦ 

0.05 

3.85 

4.07 

*  Solution:  /8-oxybutyric  acid  or  lactic  acid,  n  0.025;  hydrochloric  acid, 
N  0.02. 


ao5  oT 

A/orma//Va  o/ fi Mydroyybufaric  Ac/i^ 

Fig.  5. 


G.  E.  CuUen 


385 


The  normality  figures  in  A  and  B  do  not  represent  actual 
amounts  of  free  acid  due  to  the  presence  of  undissociated  anhy- 
dride, but  they  do  indicate  the  change  in  the  titration  curve 
caused  by  the  accumulation  of  such  acid.  Curve  C  indicates 
the  nature  of  the  decreased  reserve  in  a  dog  plasma  with  very 
low  reserve.     The  normality  figures  here  represent  actual  values. . 


0.05  O.I  O.I5 

Normolity  of  Loctic  Acid 

Fig.  6. 


Range   of  Normal    Values. 

Table  X  shows  the  variations  in  normal  plasma  in  cUfferent 
individuals  at  different  tunes.  The  values  m  a  healthy  man  may 
change  on  titration  with  one  volume  of  n/50  acid  from  a  pH  of  6.75 
to  7.00  during  the  course  of  the  day.  The  corresponding  figures 
for  titration  with  two  volumes  of  n/50  acid  are  from  a  pH  of  5.60 
to  5.90.     Dogs  have  a  lower  reserve  averaging  around  a  pH  of  5.00. 

The  normal  base  line  for  titration  with  one  volume  of  n/50 
acid  in  the  accompanying  charts  is  taken  at  7.00;  with  two  vol- 
umes at  5.6.     The  normal  limits  for  the  ''carbon  dioxide  combin- 


386 


Electrometric  Titration  of  Plasma 


ing  capacity"  is  from  55  to  70.  The  normal  alveolar  carbon 
dioxide  tension  in  mm.  is  about  38.  From  a  number  of  compari- 
sons the  ratio  between  plasma  carbon  dioxide  volume  per  cent 
and  alveolar  carbon  dioxide  tension  in  mm.  has  been  established 
as  1.45   (see  Paper  VI). 

TABLE  X. 
Table  of  Normal  Variations. 


Procedure  A 

Procedure  B. 

1  vol.  plasma  +  1  vol. 

n/50  acid. 

1  vol.  p 

asma  +  2  vol.  n 

/50  acid. 

Plasma. 

Time.* 

pH. 

Plasma. 

Time. 

pH. 

M. 

a.  m. 

6. 80 

Dog  1. 

a.m. 

4.81 

p.m. 

6.80 

p.  m. 

5.02 

V. 

May  15,  a.  m. 

7.04 

"     2. 

a.  m. 

5.18 

p.  m. 

6.89 

p.  m. 

5.24 

"      17,  a.  m. 

6. 96 

p.m. 

6.94 

"     3. 

a.  m. 
p.  m. 

4.91 
5.23 

D. 

a.  m. 

7.10 

p.  m. 

7.60 

M. 

May  18 
"     22 

5.50 
5.63 

P. 

a.  m. 

6.73 

p.m. . 

6.84 

F. 

5.69 

S. 

a.  m. 
2    p.  m. 
4 
6        '.' 

6.65 
6.74 
6.71 
6.82 

P. 

5.50 

c. 

May  19,  a.  m. 

p.  m. 

« 

"    22,    p.m. 

6.58 
6  83 
6.83 
6.85 

*  Indicates  before  and  after  meals. 


Application  of  the  Method. 

The  charts  of  diabetic  patients  followed  for  a  long  period  by  the 
electrometric  titration  of  plasma,  simultaneously  with  the  deter- 
mination of  CO2  combining  capacity  of  blood  and  plasma,  alveo- 
lar air,  and  acid  excretion^  are  given  in  Paper  VI  of  this  series. 


G.  E.  CuUen  387 

The  values  of  simultaneous  determination  of  the  "carbon  dioxide 
combining  capacity"  and  alveolar  carbon  dioxide  are  also  shown, 
since  it  was  one  purpose  of  this  series  of  observations  to  select 
the  most  suitable  method  for  determining  the  actual  amount  of 
"alkaline  reserve"  in  the  body. 

The  samples  of  blood  were  obtained  from  the  arm,  were  drawn 
through  a  McRae  needle  into  tubes  containing  a  small  amount 
of  potassium  oxalate,  and  centrifuged  at  once.  The  determina- 
tions were,  with  a  few  exceptions,  done  at  once,  but  samples 
may  be  kept  for  a  considerable  time  in  paraffined  tubes. 

The  observations  were  divided  into  two  periods;  the  first  cover- 
ing the  spring  of  1915,  the  second  that  of  1916.  The  electrometric 
titrations  on  the  first  series  were  done  by  procedure  A  — ■  1  volume 
of  plasma  +  1  volume  of  n/50  HCl;  on  the  second  series  by 
procedure  B  —  1  volume  of  plasma  +  2  volumes  of  n/50  HCl. 
This  eliminated  the  theoretical  objection  of  possible  error  due  to 
the  presence  of  carbon  dioxide,  but  proved  to  have  the  disadvan- 
tage of  lessening  the  sensitivity  of  the  titration,  in  that  for  given 
decrease  in  carbon  dioxide  combining  power  the  corresponding 
change  in  pH  was  less  than  with  one  volume  of  acid. 

CONCLUSIONS. 

The  conclusions  are  evident  from  the  charts.  The  two  methods 
of  determining  the  "alkaline  reserve"  are  entirely  comparable 
and  furnish  a  reliable  index  of  the  reserve  actually  existing  in 
the  body.  The  titration  of  the  plasma  includes  the  influence  of  all 
the  "buffers,"  not  only  the  sodium  bicarbonate,  but  also  the  pro- 
teins and  the  minute  amounts  of  phosphates.  The  fact  that  the 
electrometric  titration  of  the  plasma  gives  results  parallel  with 
the  carbon  dioxide  combining  capacity  indicates  that  the  latter 
is  proportional  to  the  total  "buffer"  content  of  the  plasma. 

SUMMARY. 

1.  The  gas  chain  method  of  determining  hydrogen  ion  concen- 
tration has  been  utilized  in  the  titration  of  plasma  and  the  con- 
ditions for  successful  operation  have  been  determined. 

2.  Values  for  normal  and  pathological  plasmas  have  been 
determined. 


388  Electrometric  Titration  of  Plasma 

3.  The  method  has  been  compared  with  that  of  the  carbon 
dioxide  combining  capacit}^  in  a  long  series  of  diabetic  patients, 
and  the  close  agreement  of  the  two  methods  has  been  estabUshed. 

BIBLIOGRAPHY. 

Auerbach,  F.,  Z.  Electrochei7i.,  1912,  xviii,  13. 

BjeiTum,  N.,  Samml.  Chem.  u.  Chem.-Tech.  Vortr.,  1915,  xxi,  1. 

Benedict,  H.,  Arch,  ges  Physiol.,  1906,  cxv,  106. 

Clark,  W.  M.,  J.  Biol.  Chem.,  1915,  xxiii,  475. 

Clark,  W.  M.,  and  Lubs,  H.  A.,  /.  Biol.  Chem.,  1916,  xxv,  479. 

Ellis,  J.  H.,  /.  Am.  Chem.  Soc,  1916,  xxxviii,  737. 

Fridericia,  L.  S.,  Berl.  klin.  Woch.,  1914,  li,  1268. 

Hasselbalch,  K.  A.,  Biochem.  Z.,  1911,  xxx,  317;  191.3,  xlix,  415;  Compt. 

rend.  Lab.  Carlsberg,  1911,  x,  69. 
Hasselbalch,  K.  A.,  and  Gammeltoft,  S.  A.,  Biochem.  Z.,  1915,  Ixviii,  205. 
Hildebrand,  J.  H.,  J.  Am.  Chem.  Soc,  1913,  xxxv,  847. 
Hoppe-Seyler,  F.,  and  Thierfelder,  H.,  Handb.   physiol.  u.  path.  Chem. 

Analyse,  Berlin,  7th  edition,  1903. 
Hulett,  G.  A.,  and  Bonner,  W.  D.,  J.  Am.  Chem.  Soc,  1909,  xxxi,  390. 
Hulett,  Physical  Rev.,  1911,  xxxiii,  307. 
von  Jaksch,  R.,  Z.  klin.  Med.,  1888,  xiii,  350. 

Lipscomb,  G.  F.,  and  Hulett,  G.  A.,  J.  Am.  Chem.  Soc,  1916,  xxxviii,  20. 
Loomis,  N.  E.,  and  Acree,  S.  F.,  Am.  Chem.  J.,  1911,  xlvi,  585. 
Lundsgaard,  C,  Biochem.  Z.,  1912,  xli,  247. 
Magnus-Levy,  A.,  Arch.  exp.  Path.  u.  Pharm.,  1899,  xlii,  149. 
McLean,  F.  C.,  and  Van  Slyke,  D.  D.,  J.  Am.  Chem.  Soc,  1915,  xxxvii,  1128. 
Michaelis,  L.,  Die  Wasserstoffionenkonzentration,  Berlin,  1914. 
Peabody,  F.  W.,  Arch.  Int.  Med.,  1914,  xiv,  236. 
Soerensen,  S.  P.  L.,  Ergebn.  Physiol.,  1912,  xii,  293. 
Stillman,  E.,  Van  Slyke,  D.  D.,  Cullen,  G.  E.,  and  Fitz,  R.,  J.  Biol.  Chem., 

1917,  xxx,  405. 
Walpole,  G.  S.,  J.  Chem.  Soc,  1914,  cvi,  2501. 
Van  Slyke,  D.  D.,  J.  Biol.  Chem.,  1917,  xxx,  347. 
Van  Slyke,  D.  D.,  and  Cullen,  G.  E.,  J.  Biol.  Chem.,  1917,  xxx,  289. 


APPENDIX. 


(pages  413-456.) 
Assembly  of  "charts  of  diabetic  patients"  referred  to  on  page 
386.     (Quoted  from  a  paper  by  Stillman,  Van  Slyke,  Cullen,  and 
Fitz;  Journal  of  Biological  Chemistry,  1917,  xxx,  413.) 


CASES 


413 


414     Blood,  Urine,  and  Alveolar  Air  in  Diabetes 

1.  Case  2481. 


Date. 

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1.  Case  2481,  female,  age  12.  Diabetic  less  than  3  months,  mild,  fair 
ability  to  burn  carbohydrate  (shown  subsequently  by  a  carbohydrate 
tolerance  test). 

The  curves  show  a  dangerous  acidosis  when  the  patient  was  placed 
on  a  fast.  This  was  accompanied  by  clinical  symptoms.  The  acidosis 
was  ameliorated  when  a  carbohydrate  diet  was  instituted.  The  drop  in 
alveolar  CO2  on  the  last  day  was  evidently  due  merely  to  change  in  res- 
piratory control. 
(From  April  30-May  21,  1915.)  Group  IV. 


THE  JOURNAL   OF   BIOLOGICAL  CHEMISTBT,    VOL.   XXX,    NO.  2 


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CASE  NO. 2680 


30 

4.  Case  2680,  female,  age  29.  Diabetic  10  months,  of  the  extremest 
type,  as  shown  by  the  inability  to  tolerate  the  1,000  calories  allowed 
although  nearly  half  of  the  caloric  intake  was  composed  of  alcohol.  A 
moderate  acidosis  was  manifested  on  admission  (October  16,  1915). 

The  curves  (taken  during   the   4th   month   of   hospital   observation) 
show  a  tendency  to  acidosis  by  continually  approaching  the  lower  border 
of  normal.     Possibly  this  is  the  result  of  the  necessarily  low  diet.     The 
alveolar  CO2  is  much  too  low  to  show  the  true  blood  bicarbonate. 
(From  February  2-21,  1916.)  Group  III. 


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C.  Case  2414,  male,  a,e  17.     Diabetic  1  yZ."  ^  ^^'ifllTJZ^l 
. T!.,t„^.  ..iHn»i«  oi  his  first  admissioniMarch  19,  1915),  lesponfleo^ 


7.  Case  UU- 


Date. 

15 

o 

1 

o 

6 

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S 

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1015 

gm.              gm.               gm. 

em. 

cc. 

mm. 

mm. XI 45 

cc. 

PH 

Mar. 

19* 

245    Fast  day  with  whiskey. 

10 

35 

17.9 

26.0 

23.8 

1.33 

20t 

560       " 

30 

80 

28.0 

40.6 

34.1 

1.22 

21 

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30 

80 

31.5 

45.7 

46.8 

1.49 

22 

525       " 

10 

75 

35.2 

51.1 

58.5 

1.66 

23 

560       " 

80 

31.5 

45.7 

52.4 

1.66 

24 

385       " 

55 

33.7 

48.9 

60.6 

1.80 

25 

35.4 

51.4 

58.0 

1.64 

26 

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43.8 

52.4 

1.73 

27 

50.4 

28 

30.6 

44.4 

29 

33.3 

48.3 

54.0 

1.62 

30 

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10 

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53.4 

1.72 

31 

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49.6 

55.2 

1.62 

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64.8 

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70 

6 

80 

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65.6 

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8 

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9 

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1.62 

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1,240 

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1,670 

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1,700 

50 

149.5 

*  Drowsiness;  hyperpnea. 
t  Drowsiness. 


426 


7.  Case  UU— Concluded. 


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ffm. 

gm. 

cc. 

mm. 

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PH 

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25 

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y- 

26 

1,835 

53 

156.5 

40 

27 

1,845 

55 

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11 

28 

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6.86 

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1 

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2 

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156.5 

40 

4 

1,985 

75.5 

162.5 

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54.0 

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1.67 

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PLASMA  COi  «  O 


6-4 


428     Blood,  Urine,  and  Alveolar  Air  in  Diabetes 


8.  Case 


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o 

Date. 

3 

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d 
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1915 

gm. 

gm. 

gm. 

cc. 

mm. 

mm.  Xl-45 

cc. 

pH 

Mar. 

18 

1,285 

41.0 

71.5 

65 

32.4 

47.0 

47.3 

1.46 

19 

1,815 

62.5 

115.0 

70 

30.0 

43.5 

20* 

1,635 

53.0 

123.0 

50 

25 

20.5 

29.7 

25.9 

1.26 

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Fast 

day. 

90 

35 

15.8 

22.9 

22*t 

(( 

a 

24.9 

(Death.) 

*  Drowsiness;  hyperpnea;  nausea. 
t  Moribund. 


Stillman,  Van  Slyke,  Cullen,  and  Fitz  429 


so   U 
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30    - 

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PLASMA     _ 
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ALVEOLAR  C02X\.45-c^ 

CASENaa293 


iB       id        20       21       22  " 

1915  MAR. 

8.  Case  2293,  male,  age  29.  Diabetic  2  years,  of  the  severest  type 
in  intolerance  of  any  food.  Complicated  at  the  end  by  pulmonary 
tuberculosis. 

The  curves  show  failure  of  response  to  large  doses  of  NaHCOs.     Death 
occurred  March  22,  1915. 
(From  March  18-22,    1915.)  Group  III-IV. 


9.  Case  2358. 


Date. 

i 

'a 
a 

o 

a 

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1 

O 

■e- 

o 

6 
o 

< 

IS 

III 

6SS  ■ 
o 

o 

oO 
cs  a 

6 

o 

> 

'a 

a 
a 

Mi 

1915 

gm. 

gvi. 

gm. 

mm. 

mm. XI. 45 

cc. 

pH 

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16 

1,915 

62.5 

178.5 

0 

37.2 

54.0 

45.8 

1.23 

17 

li 

« 

li 

18 

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19 

1,325 

49.0 

118.5 

5 

20 

« 

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21 

it 

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ii 

ii 

23 

n 

" 

24 

ii 

a 

25 

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26 

1,350 

50.0 

119.0 

10 

27 

(( 

(( 

(( 

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35.4 

51.5 

45.3 

1.28 

28 

325* 

21.0 

26.0 

29 

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30 

ti           a 

26.5 

38.4 

44.1 

1.61 

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1 

a           a 

2 

1,020 

29.0 

92.5 

10 

24.1 

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41.6 

1.73 

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1,350 

50.0 

119.0 

ii 

4 

a 

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56.8 

1.39 

6.76 

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a 

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1,375 

52.0 

a 

15 

40.7 

59.0 

57.0 

1.40 

6.73 

7 

1,495 

52.5 

131.5 

a 

8 

" 

" 

a 

a 

9 

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10 

1,535 

54.0 

132.0 

20 

11 

(( 

a 

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a 

12 

a 

a 

a 

" 

38.8 

56.3 

52.7 

1.36 

6.67 

13 

a 

a 

a 

a 

14 

1,595 

57.0 

133.0 

30 

36.8 

53.4 

55.2 

1.50 

6.76 

15 

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13.5 

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52.4 

60.8 

1.68 

6.72 

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17 

a           a 

18 

a           a 

19 

715* 

25.0 

50.0 

10 

26.2 

38.0 

45.9 

1.69 

6.41 

20 

1,035 

60.5 

80.5 

u 

21 

a 

a 

" 

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36.0 

52.2 

56.9 

1.58 

6.64 

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430 


Stillman,  Van  Slyke,  CuUen,  and  Fitz         431 


IS  27   3e2  4  6 

2913  APaW.  MA-y 

9.  Case  2358,  age  11.     Diabetic  1  year,  of  severe  type  in  intolerance  of 
any  food. 

The   curves  show  a  sudden  development  of  acidosis  on  two  separate 
fasting  periods  of  3  days  each  with  a  return  to  normal  on  the  resumption 
of  diet. 
(From  April  16-May  21,  1915.)  Group  III. 


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Stillman,  Van  Slyke,  Cullen,  and  Fitz         433 


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,Al-VEOUAR  ■ 


cAscNo.  2sa« 


10.  Case  2684,  female,  age  43. 

The  curves  show  a  continuous  low  grade  acidosis,  possibly  caused 
by  a  very  low  protein-fat  (carbohydrate-free)  diet,  necessitated  by  a 
persistent  glycosuria.  The  low  level  of  these  curves  was  subsequently 
noted  over  a  period  of  4  months'  observation.  The  acid  excretion  corre- 
sponds to  the  plasma  bicarbonate,  but  the  alveolar  CO-i  was  consistently 
very  much  too  low. 
(From  February  2-23,  1916.)  Group  III. 


a^5,'^-os 

o  o 

o  o  o 

CO    CD   Tj^' 

o  o 
ai  CO 

o  o 

O   CO 

o  o 

o 

o 

q 

05 

TJ<     -* 

":>•*■* 

CM    CM 

CO    CO 

CO  CO 

■* 

LO 

CD 

aA|,V 

o  o 
ic  CO 

o_o  o 

b-'   ■*    CD 

O    C5 

o  o 

CD  q 

CO    CO 

o 

CD 

o 

CO 

o 

CO  CO 

(N    CO    CO 

»0    lO 

O    Tt< 

Tfl     TfH 

CO 

CM 

^"^ 

o 

o  o 

lO    lO    lO 

lO    lO 

o  in 

00  o 

lO 

lO 

o 

■J9;i[  J8d  pToy 

k;~ 

CO  >o 
<M    CM 

CO    05    CO 

T— 1      I— 1      T-H 

CM    '^ 

CO    CO 

o  00 

CM    1—1 

T^  00 

o 

1—1 

00 

CO 

o 

O    05 

O    (M    CO 

C^^    Tt< 

00    1-1 

05    Tf< 

^ 

o 

00 

•ja^tl  jad  tHN 

z 

CO    l> 

lO    O   05 

^    CO 

t-  o 

O   CO 

r^ 

':*< 

05 

lO   lO 

CO    CO    kO 

03    C5 

CO    t^ 

t^  t^ 

m 

lO 

o 

O    lO 

(M    O    CO 

O    lO 

00  >re 

o  00 

en 

o 

o 

■jajTI  Jad  B9Jfi 

^ 

lO    1-1    00 

t^    03 

CT>    00 

^    lO 

^ 

o 

lO 

,-1  ^ 

CO    O    <M 

CO    CD 

OS    t^ 

O   CO 

CO 

>o 

00 

y 

<N    ^ 

—<    C<]    oq 

CM    CM 

1—1   1—1 

'"' 

O    lO 

o  o  o 

>o  o 

to   o 

o  o 

o 

^ 

in 

■sjq  fz  -lad   [OA 

ir?   >— 1 

t^    CO    00 

l^    CM 

lO    CM 

O     ^H 

1^1 

^ 

lO 

O 

,-H     CD 

— 1    00    (M 

05    ,-1 

CO   !>. 

CO    CM 

lO 

1—1 

(M    —1 

M  r-i  cq 

1-1    CM 

CO    CM 

CM    CM 

CM 

'"' 

CM 

■e02  "J^  BOl 

OO   (M 

lO  00   »o 

C^l    -* 

CO    CO 

C5    1-1 

O 

00 

O 

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g 

t^  00 

^    CO   cq 

lO   o 

-*  ^ 

IC   OO 

o 

CM 

00 

Xq  ptinoq  iqO 

■*  '^ 

CO  CO 

CM    CO 

CO    CO 

'^ 

o 

lO 

O    CO 

O    (M    t^ 

1-1    CO 

t^   CO 

CO  CO 

CM 

C<l 

CO 

■:^q3I^Al.  Xpog 

ca 

CO    iO 

iC   -^    TJ^ 

'^  ■* 

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CO    CO 

CO 

CO 

CO 

CO  CO    . 

CO   CO    CO 

CO    CO 

CO    CO 

CO    CO 

CO 

CO 

CO 

o  ~-     ^ 

w       lO 

o 

^      lO   - 

•loqooiv 

CO  -     - 

1— i 

CD 
O 

-      t^   - 

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O   2 

2^^ 

^^ 

bD 

a 

lO    O    O    lO 

o 

a 

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s 

O    i-H    <M    (M   ■- 

CO    - 

IC   o 

in 

3  -    - 

(3 
O 
o 

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tSi 

1— (    CM    lO    02 

lO 

O    CO 

lO 

r-l     r-l 

>. 

o 

^    ^ 

»o  O 

>o 

lO 

lO 

>>v,           -- 

-    ^ 

•uia^tojj 

s 

lO   O   ^   o  - 

—H     CO     4<     CO 

lO    CM 

rH     CM 

!> 

c3   -      - 
t3 

> 

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CQ     V,         V. 

0)  w      ^ 

^    ^ 

S3   -      " 

(h 

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>> 

>, 

fe 

o 

c3   ^      S 

o3   w 

03 

TS 

O    O    >0    lO 

»o  o 

TS 

o  o 

'  o 

O 

O 

O    lO 

CD    CM    t^    CM   .. 

-*    CO 

CO    -*l 

(—> 

g.      . 

CM    CM    ^ 

M 

^   CO   O   lO  ~- 

^  00 

03 

r-l     C-l 

lO 

^  »o 

o3  ::    2 

T— 1       1—1 

CM    ^ 

cs  :: 

cri 

^ 

fe 

\^ 

6 

50 

fl  cq  CO  ■<*< 

lO   CO   t^   00   o 

O   1-1 

* 

CM    CO 

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CO 

r^ 

00  05  o 

1—1    CM    CO 

1*  »o 

P 

i-s 

1— (     i-H 

T-l     rH     CM 

cq   CM   CM 

CM    CM 

434 


Stillm'an,  Van  Slyke,  Cullen,  and  Fitz         435 


& 


I- 

< 

It. 


PLASMA, 
CO2 


60^^[o^ 


W 


'''''''«'''''''''«''>«'■»''''''''■■■' 

2  3  4  5  6  7    8       10     12       X4  n       19  25-  2       4  7 

1916JAK  FEB. 

11.  Case  2684,  female,  age  43  (the  same  case  as  No.  10).     Diabetic  of 
extreme  severity  with  marked  emaciation.     A  mild  acidosis  was  present         . 
on  admission  (January  1,   1916). 

The  curves  show  a  dangerous  response  to  a  moderate  protein-fat  (car- 
bohydrate-free) diet,  which  was  accompanied  by  clinical  manifesta- 
tions of  severe  acidosis.  At  the  end  of  9  days'  fasting  the  patient  may  be 
considered  past  danger  from  an  acidosis  point  of  view,  as  is  indicated 
by  the  rise  of  the  curves.  The  curves  show  consistent  parallelism 
between  acid  excretion  and  plasma  bicarbonate. 
(From  January  2-25.  1916.)  Group  II. 


2AgV_, 

O    fO    «D 

00  "0  <» 

O    C2 

00 

lo  00 

lO    00 

to 

CC  AO   ■* 

lO     Tt<      , 

■^ 

lO  to 

0Ag,V 

o  t^  •* 
c^  00  CO 

Tt<     CO 
05    O 

o 

CO 
CO 

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CO 

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o 

(N    00   00 

o  o 

to 

00  to 

:s 

6 

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Z 

O   -*    CO 
.—1 

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t2 

o 

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(M 

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437 


13.  Case 


Date, 

M 

o 

3 

o 

d 
'S 
o 

Ph 

4J 

Carbohydrate. 

i 

8 
< 

6 
o 

> 

< 

OS  a 
0 

0 

oO 

8 

13 

a 

a 

PM 

1915 

pm. 

gm. 

gm. 

cc. 

mm. 

mm.xi.4s 

cc. 

pH 

Apr. 

7 

Green  veg.  only  containing 

15.0 

15 

32.0 

46.4 

46.3 

1.45 

6.33 

8 

«        (<       (( 

It 

20.0 

32.2 

46.7 

45.3 

1.41 

6.32 

9 

«                ((              u 

tt 

30.0 

10 

U             CI            cc 

it 

49.0 

33.5 

48.6 

49.0 

1.46 

6.55 

11* 

ii          It          it 

it 

19.0 

12 

2,440 

85.5 

224.5 

13 

2,440 

92.5 

222.0 

35.9 

52.1 

48.4 

1.35 

6.55 

14 

2,500 

97.0 

226.5 

15 

2,440 

88.0 

224.0 

38.8 

56.2 

63.1 

1.63 

6.73 

16 

2,440 

92.5 

121.5 

17 

2,440 

85.5 

224.5 

18 

Fast  day. 

19 

2,440 

92.5 

221.5 

38.0 

55.1 

54.0 

1.42 

6.70 

20 

2,440 

92.5 

221.5 

21 

2,440 

85.5 

224.5 

22 

2,420 

93.0 

219.5 

23 

2,440 

85.5 

224.5 

38.3 

55.6 

56.0 

1.46 

6.68 

24 

2,440 

92.5 

221.5 

25 

Fast  day. 

26 

2,210 

92.5 

196.5 

27 

2,210 

92.5 

196.5 

28 

2,185 

93.0 

194.5 

36.4 

52.9 

56.0 

1.53 

6.62 

29 

Fast  day. 

30 

It      it 

37.0 

53.7 

57.3 

1.55 

6.80 

May 

1 

it      it 

2 

it      It 

3 

Green  veg.  only  cc 

ntaining 

20.0 

28.7 

41.6 

45.1 

1.57 

6.46 

4 

it        it       tt 

40.0 

35.2 

51.0 

53.2 

1.52 

6.64 

5 

It        It       tt 

50.0 

6 

tt        it       it 

60.0 

32.7 

47.4 

63.0 

1.93 

6.75 

7 

it        it       it 

70.0 

36.4 

52.8 

56.0 

1.54 

8 

it        it       it 

80.0 

9 

ii        it       it 

90.0 

10 

it        it       it 

100.0 

« 

11* 

it        it       it 

24.5 

438 


IS.  Case  2S82— Concluded. 


Date. 

_o 
o 

"a 

2 

t 

1 
O 

i 

8 

6 
o 

03 

"o 

> 
< 

o 

'S  03 

03 
"5, 

o 
o 

> 

a 

03     ■     . 

1915 

gni. 

gm. 

gm. 

cc. 

mm. 

mm.  X  1.45 

cc. 

piy 

May 
12 

555 

24.0 

44.5 

10.0 

27.8 

40.3 

54.5 

1.96 

6.61 

13 

930 

43.0 

72.0 

20.0 

34.4 

49.9 

50.9 

1.48 

6.42 

14 

1,230 

47.0 

105.5 

15.0 

15 

1,370 

62.0 

113.5 

15.0 

16 

555* 

21.5 

49.0 

3.0 

17 

935* 

46.5 

80.0 

12.5 

18 

1,530 

78.0 

123.0 

15.0 

39.3 

57.3 

61.3 

1.56 

6.64 

19 

1,520 

60.5 

130.5 

15.0 

20 

1,450 

70.0 

123.5 

3.5 

21 

1,430 

71.0 

122.5 

22 

1,425 

60.5 

127.0 

37.7 

54.7 

62.3 

1.65 

6.76 

23 

Fast  day. 

24 

1,425 

53.0 

130.0 

35.6 

51.6 

60.6 

1.70 

6.83 

*Partial  fast. 


PLASMA 
'    C02     - 


ALVEOLAR 


CASE  N0.23eZ 

1 1  i,m  luj  I  Nj  I  ij  M  I  111  1 1 1  m  1 1 1 1 1  It  I  n  I  i.Li  I  III 


^ 


4i 


ii"^^^ 


7    io  J3  15     19     23 


8303     6 

MAY 


2^ 


13,  Case  2382,  male,  age  40.     Diabetic  8  years,  severe  in  intolerance  of 
food,  with  a  tendency  to  a  low  grade  chronic  acidosis. 

The  curves  are  peculiar    in  that  they  are    high    during  a  period  of 
relatively  high  fat  feeding,  and  show  an  unstable  and  low  level  during  a 
carbohydrate  tolerance  test,  due  perhaps  to  the  4  days'  fast  which  pre- 
ceded this  test. 
(From  April  7-May  24,  1915.)  Group  III. 

439 


440     Blood,  Urine,  and  Alveolar  Air  in  Diabetes 


H.  Case 


Date. 

1 

2 

-^ 

£ 

1 

O 
u 

05 
O 

o 
o 

< 

6 
o 

< 

.^  So- 

o  g'S 

52  3 

c5 

•^  03 

q 

"a 

o 
o 

> 

a 
a 

PL, 

ms 

gm. 

gm. 

gm. 

cc. 

mtn. 

mm.  XI 46 

ce. 

PH 

Mar. 

25 

1,720 

91.5 

58 

30 

97.5 

44.7 

64.8 

64.6 

1.22 

26 

1,725 

85.5 

61 

a 

tt 

27 

n 

91.5 

58.5 

It 

28 

682    Fast  day. 

tt 

29 

2,180 

111.0 

99.0 

30 

" 

30 

2,215 

111.5 

102.5 

tt 

tt 

33.3 

48.3 

42.7 

1.28 

31 

2,250 

112.5 

105.5 

It 

" 

Apr. 

1 

2,215 

112.0 

102.5 

tt 

tt 

38.6 

55.8 

54.4 

1.41 

2 

2,385 

114.0 

115.0 

40 

tt 

44.6 

64.7 

54.4 

1.22 

3 

it 

« 

(( 

it 

" 

45.9 

66.6 

61.6 

1.34 

4 

700    Fast  day. 

100.0 

5 

2,370 

116.0 

111.0 

40 

It 

6 

2,410 

114.0 

116.0 

tt 

7 

2,890 

115.0 

167.0 

tt 

42.9 

62.2 

52.4 

1.22 

6.46 

8 

2,660 

(( 

« 

67.5 

9 

1,920 

88.0 

150.0 

47.6 

69.0 

61.0 

1.28 

6.92 

10 

1,975 

86.0 

156.5 

11 

157    Fast  day. 

22.5 

12 

1,975 

87.0 

156.5 

40 

13 

2,025 

90.5 

156.0 

50 

47.6 

69.0 

60.6 

1.27 

6.60 

14 

2,060 

90.0 

160.0 

It 

15 

2,085 

91.5 

173.5 

tt 

46.8 

67.7 

59.5 

1.27 

6.69 

16 

2,145 

90.5 

169.0 

tt 

17 

2,095 

89.0 

164.0 

tt 

18 

Fast  day. 

19 

2,035 

91.5 

156.5 

50 

40.1 

58.2 

51.4 

1.28 

6.78 

20 

1,975 

89.0 

155.5 

40 

21 

2,010 

79.0 

174.5 

tt 

22 

1,955 

89.0 

153.5 

tt 

23 

1,945 

87.5 

(( 

It 

43.5 

63.1 

63.1 

1.46 

6.84 

24 

1,975 

90.0 

155.5 

tt 

25 

Fast  day.                            | 

26 

1,970 

90.0 

161.0 

25 

27 

2,000 

ti 

165.0 

tt 

28 

2,165 

93.5 

180.5 

tt 

43.6 

63.2 

59.0 

1.35 

6.58 

29 

2,110 

93.0 

175.0 

tt 

30 

2,140 

92.5 

178.5 

tt 

43.7 

63.4 

64.9 

1.49 

6.74 

Stillman,  Van  Slyke,  Cullen,  and  Fitz  441 


Coi 

]pH 

no 

65 

AtVEOLAR  co^Vi.4j  n\           \            ^                PLASMA     ^ 
-  6-8           <*.               /\.    //  \           \    j^    \         f„  *^^2       ■ 

60 

-«*  \  ]\lt\KS4^' 

5f 
50 

\   l\ \        \  / 

"-     \\f            "^ 

45 

.6.0      Y 

40 

-.5.5 

1  1  1  1  1  1  1  1  1  1  1  1  !  1  1  M  1  1  M  r  J  1  t  1  1  1  1  1  1  !  1  I  p  i^ASE  f^*  ^3     2. 

air      301s       7S      2315    19    23       2Qad 

1^15  m?;.     APRIL. 

14.  Case  2332,  age  42._    Diabetic  8  years,  of  mild  type,  complicated  by 
furunculosis  and  carbunculosis. 

During  the  period  over  which  the  chart  is  drawn,  the  patient  suffered 
a  rather  intense  gastrointestinal  upset  of  unknown  origin.  This  is  re- 
flected in  the  instability  of  the  curves.  Following  the  recovery  from 
this  attack,  the  curves  continue  on  a  high  lerel  up  to  the  time  of  discharge 
from  the  hospital. 
(From  March  25-April  30,  1915.)  Group  I. 


15.  Case  234S. 


Date. 

o 

"3 

"3 
1 

c 
S 
2 

1 

>, 

O 

u 

o 

§ 

< 

6 
o 

< 

0 

6 

■ft 

6 
0 
> 

"3 

a 

a 

1-10 

Ah 

1916 

gm. 

gm. 

gm. 

cc. 

mm. 

mm.  X  i.iS 

CC. 

VH 

Mar. 

30 

1,940 

98.5 

83.5 

15.0 

100 

36.2 

52.2 

60.5 

1.67 

31 

1,940 

80.5 

91.0 

a 

100 

33.9 

49.2 

47.8 

1.41 

Apr. 
1 

1,965 

100.0 

84.0 

20.0 

100 

37.1 

53.8 

51.6 

1.39 

2 

1,965 

82.0 

91.0 

<t 

100 

3 

1,970 

89.5 

88.0 

ii 

100 

34.4 

49.9 

58.2 

1.69 

4 

1,960 

97.0 

84.5 

u 

100 

5 

2,235 

108.5 

109.0 

19.0 

100 

6 

2,245 

120.0 

104.5 

20.0 

100 

39.3 

57.0 

52.0 

1.32 

7 

2,240 

102.0 

112.0 

it 

100 

36.4 

52.8 

51.4 

1.41 

8 

2,065 

102.0 

112.0 

te 

75 

38.8 

56.2 

49.3 

1.27 

6.57 

9 

1,490 

97.5 

104.0 

30.0 

10 

1,510 

98.5 

105.5 

t( 

39.3 

57.0 

56.0 

1.42 

6.58 

11 

210 

Fast  day. 

30 

12 

1,725 

97.5 

129.5 

30.0 

13 

1,955 

90.0 

157.5 

39.8 

57.7 

54.0 

1.36 

6.69 

14 

1,970 

92.0 

158.5 

15 

2,205 

92.0 

183.5 

39.5 

57.3 

55.0 

1.39 

6.66 

16 

2,090 

97.0 

179.5 

17 

2,085 

89.5 

182.5 

18 

Fast  day. 

19 

2,215 

90.0 

180.5 

40.0 

39.3 

57.0 

58.5 

1.49 

6.82 

20 

2,745 

104.0 

231.5 

21 

2,730 

95.0 

234.0 

22 

2,715 

102.5 

229.0 

23 

2,710 

101.5 

229.0 

36.9 

52.5 

55.2 

1.50 

6.68 

24 

2,715 

102.5 

230.0 

25 

Fast  day. 

26 

2,665 

97.0 

231.0 

30.0 

27 

2,655 

97.0 

230.0 

28 

2,775 

90.0 

245.5 

36.4 

52.8 

54.4 

1.49 

29 

2,755 

96.5 

240.5 

30 

2,760 

92.0 

243.0 

38.0 

55.1 

59.0 

1.55 

6.70 

31 

2,735 

94.0 

239.0 

May 

1 

Fast  day. 

2 

2,760 

93.5 

242.0 

30.0 

3 

2,780 

97.0 

243.0 

i( 

4 

2,930 

101.0 

257.5 

ce 

40.8 

59.2 

55.4 

1.36 

6.7G 

5 

3,0§0 

104.0 

273.5 

it 

6 

3,090 

104.0 

273.5 

« 

7 

2,580 

100.5 

220.0 

(( 

442 


Stillman,  Van  Slyke,  Cullen,  and  Fitz  443 


-02 


^H 


65>-6d 


jaH+lHcl 

ALVEOLAR 

PUASMA 
— CO2 


45  -6.0 


40 -SS 


CASE  NO.  2343 


so  i  3    6  e  10  is  16    19    zi 


iSlS^iAR.      APRIL 


26^       * 

MAV 


15.  Case  2343,  male,  age  44.     Diabetic  9  years,  mild  in  type,  without 
evidence  of  acidosis  before  the  institution  of  active  treatment. 

The  curves  show  an  unstable  and  rather    low    level,    following  a  2 
months'  period  of  very  low  diet,  and  a  gradual  rising  and  uniformity  of 
the  curves  when  the  patient  was  placed  on  an  adequate  diet. 
(From  March  30-May  4,  1915.)  Group  I. 


16.  Case  2128. 


Date. 

i 

la 

a 
'S 
o 

d 

fe 

6 

"S 

-d 
>> 

J3 
o 

.Q 
OS 

O 

o 
o 

K 

6 
o 

03 

> 

< 

o 

o 

oO 
■-3  cj 
ca  a 

0. 

c5 
o 

"3 

H 
S 

■-HO 

1915 

em. 

gm. 

gm. 

gm. 

mm. 

mm.X1.4S 

cc. 

PH 

Apr. 

15 

2,040 

142 

145 

26.5 

20 

35.9 

52.1 

54.0 

1.50 

6.53 

16 

2,830 

202.5 

204 

26.0 

« 

36.4 

52.8 

51.4 

1.41 

6.72 

17 

2,780 

155.0 

223 

18.0 

(( 

18 

1,845 

129.0 

133 

19.0 

« 

19 

1,370 

47.0 

104.5 

50.5 

(t 

20 

Fast  day. 

It 

21 

a        a 

10 

22 

2,005 

8.0 

201.5 

24.0 

40.8 

59.2 

57.5 

1.41 

6.72 

23 

2,225 

32.5 

186.0 

89.5 

24 

2,430 

40.5 

202.0 

95.0 

25 

1,000 

39.0 

58.0 

74.0 

26 

Green  veg.  on 
taining 

ly  con- 

75.0 

27 

a 

38.3 

55.5 

54.0 

1.41 

28 

1,855 

2.6 

155.5 

75.0 

29 

a 

i( 

t( 

a 

30 

930 

0 

100.0 

0 

38.7 

56.1 

58.8 

1.52 

6.92 

May 

1 

1,440 

29.5 

.  141.5 

1.0 

2 

1,450 

30.5 

142.0 

" 

31.3 

45.4 

45.1 

1.44 

6.49 

3 

1,075 

i( 

102.0 

" 

4 

1,040 

26.0 

100.0 

« 

38.0 

55.1 

48.6 

1.28 

6.55 

5 

815 

24.0 

80.0 

" 

6 

1,095 

37.0 

78.0 

54.0 

42.0 

60,9 

57.0 

1.36 

6.78 

7 

Fast  day. 

8 

1,095- 

32.5 

67.0 

83.0 

9 

1,075 

33.0 

66.5 

67.5 

10 

1,060 

29.0 

66.0 

81.0 

11* 

175    Fast  0 

ay. 

12 

870 

26.5 

44.0 

86.5 

38.8 

56.3 

51.8 

1.35 

6.60 

13 

930 

32.5 

40.0 

104.0 

14 

875 

29.5 

40.0 

93.0 

15 

1,180 

45.0 

45.5 

140.0 

16 

465 

0 

50.0 

0 

17 

1,130 

43.5 

46.5 

124.5 

18 

950 

42.0 

29.0 

123.5 

39.3 

57.0 

51.9 

1.32 

6.57 

*Alcohol,  25  cc. 


444 


Stillman,  Van  Slyke,  CuUen,  and  Fitz         445 


€5 
60 


..68 


66 


55""6-4 


SO' 


6-2 


4ff-eo 


I  ii_i  Hi  III  i'i_L"J'iM'  L«  ""_L'  "" 


t9lS"AP!ilL. 


'A";^'i'4'^""'A""'i'a 


|3H+1HC| 

AUV POLAR 
COaJ^'-^S" 

PLASMA 


CASE  NO.  a  12  6 


MAY 


16.  Case  2128,  female,  age  18.     Diabetic  3  years,  of  severe  type  in  in- 
ability to  metabolize  carbohydrate  or  fat,  though  maintaining  a  fair  state 
of  nutrition  and  strength. 
(From  April  15-May  18,  1915.)  Group  III-IV. 


oy^^^-m 

00 

o 
3 

CO 

CO 

lO 

C3 

CO 

CO 
lO 

56.5 

CO 

aA§)V 

00 

o 

00 

00 
1-1 

CO 

CO 
est 

d 

i 

•jo^ij  wd  pToy 

<= 
^ 

1-H 

o 
1— 1 

g 

O 

00 

00 

CO 

CD 
1— 1 

r-H 

t3 

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o 
^ 

CO 

in 

lO 

lO 

o 

CO 

CD 

1 

■jajij  lad  Baifi 

CO 

co" 

eo" 

o 

CD 

o 
00 

lO 

00 
CO 

co" 

o 
o 

lO 
CO 

co" 

•gjq^3i9d-iOA 

s 

CO 

T-l 

§         - 

O 

05 

lO 
CO_^ 

lO 

1 

lOH 

09/N            lOA 

00 
CO 

CO            CO 
lO           lO 

CO 

00 

CO 
CO 

id 

CO 
CO 

to 

LO 

ajoqAV  00  001 
Aq  punoq  ^00 

^ 

CO 

o        00 

t^          CO 

o 

lO 

CD 
CD 

■* 

^ 

CO 

'00  '^1'^   nun 


ZQO  ■EOISBld 


-ffBid    00  GOT 
iCq  pnnoq  iqO 


=00  -iBlosAi  V 


■%v[2i3M.  jtpog 


■a^BjpXqoqiBQ 


■^^^ 


araiojj 


•99UOJB0  i^^ox 


fe 


5     ^    (M    CO 

fa 


l>.   00    Oi    O    >— I    M 


446 


rt*    lO   CO   t^    00    05 


Stillman,  Van  Slyke,  CuUen,  and  Fitz  447 


coz 
ear 


h5-5 


60 

55  f53 


SO 
45 

40 


-5.1 


PLASMA 
C02 


)3H+2HCl 


BLOOD 


I     I     I     I     I     I     I. 


I     I     1     I     I    I     I     I  ,1.    I     I     I 


2       4  7 

5916  FEB. 


COj 

65 

eo 

55 
50 
45 
40 
35-J 


Qo-i^ 


Plasma 

COg 


ALVgOLAK 

eo2>«i-45 


CASK  MO.g'^O© 


. „.j 


17.  Case  2480,  female,  age  28.  Diabetic  5  years,  formerly  of  a  mild 
type,  but  latterly  developing  into  an  obstinately  progressive  form,  with 
emaciation  and  inability  to  tolerate  calories  enough  to  maintain  existence 
in  an  aglycosuric  state.  A  low  grade  acidosis  has  been  present  for  15 
months  of  observation. 

During  the  period  shown  the  patient  was  temporarily  free  from  acidosis 
as  the  result  of  unusual  response  to  treatment.     The  acid  excretion  cor- 
responds to  the  plasma  bicarbonate,  but  the  alveolar  CO2  is  consistently 
too  low. 
(From  February  2-21,  1916.)  Group  IIL 


OA^\-08 

00 

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CO 

O 

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o 

o 

lO 

ci 

CO 

CO 

00 

03 

t^ 

CO 

CO 

t^ 

t^ 

1> 

t^ 

t^ 

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M 

00 

T)< 

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00 

o 

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o 

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00 

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CO 

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^ 

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00 

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CO 

00 

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z 

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o 

O 

Q 

to 

o 

ira 

o 

o 

t^ 

CO 

c^ 

CO 

CO 

o 

lO 

^ 

lO 

TfH 

o 

g 

CO 

CO 

'-' 

^ 

^ 

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o 

o 

IC 

lO 

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lO 

lO 

'^ 

lO 

t^ 

l^ 

05 

-* 

CO 

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g 

t- 

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C^ 

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oq 

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lOH  OSA 

a; 

00 
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t^ 
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§ 

00 

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lOAg  +  BrasBid; 

a 

lO 

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lO 

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„lZre  pooiq 

l> 

(M 

CO 

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05 

00 

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CD   t^    00 

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T-H     OQ 

CO    ■*    lO 

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o 


448 


coa 


1>H 


90 

85  -59 
80 
75  -5.7 
70 
65  SS 
60 
55-5.3 
50 
45  51 


^H+2HCl 


PLASMA 
CO  2 


>  BLOOD 


■t-Ht- 


I     I     I     I     I     I     ,1 


CO5 

75-- 
70- 
€5- 

60- 

55- 
SO- 

45- 

4oL- 


1916  FEB. 


9      II 


14     1€ 


ao-|v7lc 


/^ 


PLASMA 
CO2 


LVEOLAR 
C02«l-*5 


CASS  NO.  223-* 


449 


19.  Case  237 J^. 


Date. 

i 

'u 
O 

o 

a 

o 

PL, 

Fat. 
Carbohydrate. 

6 
o 

-3 
"o 

o 
_> 

< 

>1   CO 

SI   s 

c5 
"a 

0 

0 

> 

"3 

a 

1915 

gm. 

gm.             gm. 

mm. 

mm.  X  H5 

cc. 

PH 

Apr. 

15 

Green  veg.  only  containing]       10 

41.0 

59.5 

55.4 

1.35 

6.77 

16 

<(        ((      (( 

It                    11 

17 

«        ((      (( 

it                      et 

18 

Fast  day. 

19 

700 

25 

.  57.5         1 

5 

40.8 

59.2 

56.4 

1.38 

6.80 

20 

1,190 

44.5 

101.7 

21 

« 

ii 

tt              i 

22 

1,380 

63.5 

114.0 

23 

(( 

it 

it              t 

39.8 

57.8 

33.4 

1.34 

6.72 

24 

1,325 

65.0 

107.5 

25 

Fast  day. 

26 

1,550 

65.5 

131.5         1 

5 

27 

1,605 

64.0 

138.0 

( 

28 

1,530 

66.0 

130.0 

' 

37.7 

54.7 

59.0 

1.57 

6.53 

29 

(( 

a 

"              ' 

< 

30 

1,595 

(< 

136.0 

I 

May 

•1 

1,540 

73.5 

126.5 

I 

2 

Fast  day. 

3 

1,625 

75.0 

133.0         2 

0 

40.8 

59.2 

61.8 

1.51 

6.85 

4 

1,665 

(( 

137.0 

' 

5 

1,705 

67.5 

145.5 

t 

6 

2,090 

76.0 

182.0 

' 

41.0 

59.5 

63.6 

1.55 

7 

1,975 

72.5 

175.0         1 

3 

8 

1,820 

68.5 

165.5 

0 

9 

Fast  day. 

10 

1,910 

66.5 

169.5         1 

5 

11 

503* 

20.5 

44.0 

2 

12 

Fast  day. 

13 

ii        ti 

41.4 

60.0 

57.7 

1.39 

6.80 

14 

U                 tl 

15 

675* 

32.5 

54.0         1 

0 

40.4 

58.6 

59.0 

1.46 

6.75 

16 

1,040 

45.0 

98.0 

17 

1,250 

63.5 

102.5 

18 

" 

(( 

(( 

40.0 

58.0 

58.3 

1.46 

6.57 

19 

« 

(f 

tt 

20 

1,260 

72.5 

99.5 

21 

1,575 

75.0 

132.0 

22 

1,805 

83.5 

153.5 

23 

Fast  day. 

24 

1,570    1     57.0 

140.0  1       1 

0 

40.4 

60.0 

58.5 

1.41 

6.71 

*Partial  fast. 


450 


StillmaD,  Van  Slyke,  Ciillen,  and  Fitz         451 


COj, 


f>H 


70  1-0 
65- 6-6 

55- S  4 


V) 


pH*mcU 


VEOLAg  COa. 


" — ^ 


PLASMA „ ^ 
C02     ~  Q 


CASE  NO.  2  37^ 


.1'  '  '1'  "J  '  I  Ml  I  I  I  1  I  I  I  M  I  I  It  1 1  I  I  I  I  I  H  I  I  I  I 
IS      19      23       2d     I  3     6  IS  15    Id  24 

19I5APRIU  MAV 


19.  Case  2374,  age  61.  Diabetic  11  years,  of  a  mild  type,  apparently 
arrested  until  the  year  before  admission,  when,  following  a  physical  shock, 
the  patient  showed  signs  of  marked  acidosis. 

The   curves    illustrate    the   absence    of  acidosis    in    a  mild  diabetic 
responding  satisfactorily  to  treatment. 
(From  April  15-May  24,  1915.)  Group  I. 


20.  Case  2389. 


Date. 

0 
H 

'S 

S 

a 
t-, 

>, 

0 

c« 
0 

6 
0 

0     . 
0  0  ri 

0 

0 

6 
0 

> 

"a 

a 

E 

as  J,    ■ 

P4 

191!^ 

gm. 

gm. 

ff7ra. 

mm. 

mm.X14S 

CC. 

pi/ 

Apr. 
14 

1,805 

46.5 

165 

20 

38.8 

56.2 

58.5 

1.51 

6.50 

15 

1,860 

50.0 

i< 

30 

16 

1,815 

56.5 

ii 

20 

40.7 

59.0 

62.6 

1.54 

6.75 

17 

1,795 

" 

163.5 

« 

18 

Fast  day. 

19 

1,910 

46.0 

176.5 

20 

37.2 

53.9 

57.5 

1.55 

6.58 

20 

a 

a 

a 

« 

21 

u 

" 

a 

a 

37.1 

53.8 

61.6 

1.66 

6.65 

23 

a 

i< 

(f 

a 

24 

11 

a 

<( 

" 

25 

Fast  day. 

26 

1,910 

46.0 

176.5 

20 

27 

(( 

it 

it 

(( 

28 

2,040 

60.0 

185.0 

a 

29 

2,025 

67.0 

180.5 

« 

39.0 

56.6 

67.2 

1.72 

6.99 

30 

u 

it 

(( 

« 

May 

1 

1,910 

66.0 

167.5 

« 

2 

Fast  day. 

3 

4 
5 

1,995 

70.0 

170.0 

30 

36.5 

53.0 

58.7 

1.61 

6.81 

1,990 

61.0 

173.5 

6 

2,020 

60.0 

177.5 

7 

2,025 

81.0 

168.5 

39.3 

57.0 

58.8 

1.50 

8 

2,020 

70.5 

173.0 

9 

Fast  day. 

• 

10 

2,020 

70.5 

173.0 

30 

11 

2,045 

80.0 

171.0 

" 

12 

2,040 

62.5 

178.5 

u 

37.9 

55.0 

57.0 

1.50 

6.79 

13 

1,920 

65.5 

169.0 

20 

14 

1,930 

69.5 

172.5 

a 

36.1 

52.4 

59.0 

1.63 

6.62 

15 

(( 

(f 

u 

" 

16 

400* 

20.0 

34.0 

17 

Fast  day. 

18 

i(             u 

19 

1,450  =• 

34.0 

136.0 

11 

32.5 

46.4 

.  58.2 

1.82 

6.62 

20 

1,805 

45.0 

168.0 

15 

21 

u 

(( 

<( 

(I 

41.0 

59.5 

60.6 

1.48 

6.69 

*Partial  fast. 


452 


Stillman,  Van  Slyke,  Cullen,  and  Fitz  453 


COg^ 

^H 

lo 

-lO 

A^ 

H 

6S 
60 

^ 

s/ 

\ 

5      pH+lHcl=x 

55 

-6.4 

r 

\  ^- 

--^. . 

7^ 

lAusf  Solar     ^ 

V-^^ 

V 

\ 

f-    C_C>2.^'    ^^ 

5o 

"62 

A 

^ 

45- 

-60 

• 

U 

40 

U ' 

1  M 1  III  1  II 

1 II 11 1 II 

III  M 

11  III 

.,,,      CASEN0.2389 

i4! 

li  a 

29 1  i 

7 

iiw 

19  ii 

(9I5APRIU 


MAY 


20.  Case  2389,  male,  age  35.     Diabetic  4^  years,  of  moderate  severity 
as  shown  by  low  tolerance  for  carbohydrate. 

The  curves  show  the  absence  of   acidosis   in  a  case    which  responds 
satisfactorily  to  treatment.     The  alveolar  CO2  following  fasting  on  May 
18-19,  shows  on  the  19th  a  false  drop,  due  not  to  fall  in  blood  bicarbonate, 
but  to  the  nervous  effect  of  fasting. 
(From  April  14-May  21,  1915.)  Group  I. 


454    Blood,  Urine,  and  Alveolar  Air  in  Diabetes 


21.  Case 


Date. 

i 

o 

q 
'3 

o 

-5 
>, 

o 

-s 

as 
O 

6 
o 

S 

1 

< 

62  a 
u 

Ratio 
plasma  COi 
mm.  alv.  CO2 

—10 

iSlS 

gm. 

gm. 

gm. 

mm. 

mm.XHt 

cc. 

vH 

Apr. 

1 

1,175 

34.5 

50.0 

150.0 

43.6 

63.2 

63.2 

1.45 

2 

(( 

(( 

« 

It 

3 

4 

1,300 

40.5 

45.0 

175.0 

45.9 

66.7 

69.8 

1.52 

5 

Fast  day. 

6 

785 

29.0 

61.5 

25.0 

42.1 

61.1 

59.1 

1.40 

7 

1,290 

50.0 

106.0 

(( 

37.7 

54.7 

49.4 

1.31 

6.59 

8 

1,425 

70.0 

111.5 

tt 

44.6 

64.7 

46.3 

1.04 

6.47 

9' 

1,780 

69.0 

150.0 

t( 

41.7 

60.5 

56.4 

1.35 

6.92 

10 

« 

" 

it 

" 

11 

Fast  day. 

12 

2,110 

76.0 

171.5 

50.0 

13 

2,105 

68.5 

174.0 

46.1 

66.9 

60.6 

1.31 

6.52 

14 

2,100 

74.5 

171.0 

tt  , 

15 

2,545 

71.0 

220.0 

43.2 

62.6 

59.5 

1.38 

6.60 

16 

2,585 

76.5 

221.0 

17 

2,575 

69.5 

224.0 

18 

Fast  day. 

19 

2,615 

84.5 

223.0 

50 

45.1 

65.4 

62.6 

1.39 

6.90 

20 

2,620 

77.0 

226.0 

21 

2,640 

80.0 

228.5 

- 

22 

2,660 

86.0 

226.0 

23 

2,710 

95.5 

217.5 

45.7 

66.3 

62.1 

1.36 

6.71 

24 

2,715 

85.0 

232.5 

25 

Fast  day. 

26 

2,590 

84.0 

219.5 

50 

27 

2,525 

77.5 

215.0 

it 

28* 

2,205 

74.0 

184.0 

21 

42.9 

62.2 

61.6 

1.44 

29 

Fast  day. 

30 

1.735** 

60.5 

161.0 

22 

41.5 

60.2 

60.3 

1.45 

6.86 

May 

1 

2,385 

80.5 

210.5 

25 

2 

Fast  day. 

3 

2,380 

80.0 

210.0 

25 

4 

2,370 

79.0 

209.0 

tt 

46.6 

67.6 

65.9 

1.41 

6.91 

*Alcohol,  15  cc. 
♦♦Partial  fast. 


Stillman,  Van  Slyke,  Cullen,  and  Fitz         455 


PUASMA     ^ 

//       coz.     "  O 


/kcAl-VEOUAR     C02.X(  4-5 


45   -6.0 


40  -  5-8 


III  Mil  I  III  11  II  lllll  I  MM  Ml.llll  IJL 

i    3    6     d     19  IS     19     23       2830     4 


CASE  NO.  239'4 


ld»5  APRIU 


MAf 


21.  Case  2394,  male,  age  30.     Diabetic  1?  years,  of  mild  type  without 
any  evidence  of  acidosis. 

The  chart  shows    a  fall    in  the  curves  to  below  normal  during  the 
period  of  adjustment  following  a  high  carbohydrate  diet.     Following  this 
period  the  curves  remained  normal  throughout. 
(From  April  1-May  4,  1915.)  ■  Group  I 


456    Blood,  Urine,  and  Alv6olar  Air  in  Diabetes 


65-1 


6« 


6o< 


55  ■«4- 


So--e-2 


45.^0 


40.. 


35 -se 


30 


2^ 


-54 


rpLASMA 
CO  2^ 

CASE  N0.23«6 
I  >  I  I  I  I  I  I  I  I  I  I  I  M  I  I  I  I  I  I  I  I  I  I  I  I  I  I  I  I  1  I  I  I  M  I  I  I  I  I  I  I  I  I  I  I  II  IjJ  I  l_ 


n  14     J8  21 


El  29 

IdlS    MAR. 


APRIL 


14 


1921 


2d 


2        7 


22.  Case  2366,  male,  age  26.  Lobar  pneumonia,  empyema,  acute  ne- 
phritis. Acute  nephritis  was  discovered  February  12,  1915,  during  con- 
valescence from  a  severe  attack  of  lobar  pneumonia  followed  by  empyema. 
Typical  course  of  severe  acute  nephritis  with  evidence  of  marked  change 
in  renal  function  followed  recovery. 

The  chart  shows  the  curves  in  a  patient  with  the  acidosis  of  acute 
nephritis,  with  return  to  normal  as  renal  function  improved.  These 
curves  are  of  especial  interest  because  they  show  an  effect  of  disease  on 
respiration  exactly  opposite  to  that  often  encountered  in  severe  diabetes. 
The  alveolar  CO2  was  consistently  much  too  high  to  indicate  the  real  ex- 
tent to  which  the  alkaline  reserve  was  lowered. 
(March  21-May  21,  1915.)  Nephritic. 


VITA. 

Glenn  Ernest  Cullen  was  born  April  1,  1890,  at  Isle  St. 
George,  Lake  Erie,  Ohio.  He  attended  the  public  schools,  passed 
the  Boxwell  Patterson  examinations  for  a  high  school  scholar- 
ship, and  graduated  from  Sandusky  (Ohio)  High  School  in  1907. 
He  entered  the  University  of  Michigan  in  1908  and  was  gradu- 
ated in  1912  with  the  degree  of  A.B.  He  returned  to  the  same 
University  for  graduate  work  in  chemistry  and  engineering,  and 
obtained  the  degree  of  B.Ch.E.  in  1913. 

At  the  University  of  Michigan  he  was  assistant  in  Qualitative 
Analysis  1910-12,  and  teaching  assistant  in  General  Chemistry 
1912-13,  and  was  elected  to  Phi  Lambda  Upsilon  and  to  Sigma  Xi. 
He  has  been  on  the  Scientific  Staff  of  The  Rockefeller  Institute 
1913-17,  and  is  now  an  Associate  in  the  Physiological  Chemistry 
Laboratory  of  The  Rockefeller  Institute  Hospital.  He  is  a 
member  of  the  American  Chemical  Society  and  of  the  American 
Society  of  Biological  Chemists. 

He  matriculated  in  the  Faculty  of  Pure  Science  of  Columbia 
University  in  1914. 

He  has  collaborated  in  the  following  publications: 
The  Mode  of  Action  of  Urease  and  of  Enzymes  in  General, 

D.  D.  Van  Slyke  and  G.  E.  Cullen, 

Jo^ir.  Biol.  Chem.,  1914,  xix,  141. 
A  Permanent  PrepareAion  of  Urease,  and  Its  Use  in  the  Determination  of 
Urea, 

D.  D.  Van  Slyke  and  G.  E.  Cullen, 

Jour.  Biol.  Chem.,  1914,  xix,  211. 
The  Determination  of  Urea  by  the  Urease  Method, 

D.  D.  Van  Slyke  and  G.  E.  Cullen, 

Jour.  Biol.  Chem.,  1916,  xxiv,  117. 
The  Amino-Acid  Content  of  the  Blood  and  Spinal  Fluid  of  Syphilitic  and 
Non-Syphilitic  Individuals, 

A.  W.  M.  Ellis,  G.  E.  Cullen,  and  D.  D.  Van  Slyke, 

Jour.  Amer.  Med.  Assoc,  1915,  Ixiv,  126. 
The  Urea  Content  of  Human  Spinal  Fluid  and  Blood, 

G.  E.  Cullen  and  A.  W.  M.  Ellis, 

Jour.  Biol.  Chem.,  1915,  xx,  511. 
The  Formation  of  Urea  in  the  Liver, 

D.  D.  Van  Slyke,  G.  E.  Cullen,  and  F.  C.  McLean, 

Proc.  Soc.  E.v.per.  Biol,  and  Med.,  1915,  xii,  93. 
The  Nature  and  Detection  of  Diabetic  Acidosis, 

D.  D.  Van  Slyke,  E.  Stillman,  and  G.  E.  Cullen, 

Proc.  Soc.  Exper.  Biol:  and  Med.,  191.5,  xii,  165. 


COLUMBIA   UNIVERSITY 

This  book  is  due  on  the  date  indicated  below,  or  at  the 
expiration  of  a  definite  period  after  the  date  of  borrowing, 
as  provided  by  the  rules  of  the  Library  or  by  special  ar- 
rangement with  the  Librarian  in  charge. 

DATE  BORROWED 

DATE  DUE 

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DATE  DUE 

C2a(638)MS0 

QP91 


C89 


Cullen 
The  electronetricJtiir&i.iDrL_QiL.±li£ 


